TB or Not TB: The Weirdness that is Extra-Pulmonary Tuberculosis

I like wild plot twists in my novels, remixes of my favorite songs and food with unexpected, exotic flavors. Needless to say, I also love hearing of cases where an infectious disease takes an unpredictable turn, appearing where it traditionally does not. We have quite the curve-ball with Mycobacterium tuberculosis, a microbe with itinerant tendencies that materializes in some surprising anatomical locales.

Patient Richard Pendlebery with extrapulmonary tuberculosis infection of the joints. He's dapper aside from the flipper, no? Photograph taken by William H. Rhoads in Philadelphia circa 1866-98. Property of the College of Physicians of Philadelphia and the Mutter Museum. Click for source.

Tuberculosis (TB) is in the big league of the leading infectious diseases that cause profound morbidity and mortality throughout the world. We all know this, yes? When we think of TB, we think of the frail poet John Keats, sticky handkerchiefs, bloody loogies, and wracking wet coughs. But for a microbe that we customarily associate with the lungs, this guy can really do a corporeal tour, appearing in such disparate locations as the spine, joints, intestines, and skin. In fact, it’s not that uncommon. Extra-pulmonary TB (EPTB) is responsible for 15 to 20% of all cases of TB, and can increase to up to 50% for those who are severely immunocompromised, as is the case with AIDS patients (1).

We often think of microbes and parasites as uniquely adapted to whichever locale in which they cause disease. But TB can be rather laissez faire about its home base as it lives rather comfortably within the peripatetic macrophage. Following inhalation of the rod-shaped microbe, the bacterium is phagocytized by a macrophage in the alveoli of the lung, which can then travel into the blood stream or into the lymph nodes via lymph. This so-called “lymphohematogenous seeding” of the bacteria spreads the microbes from their pulmonary location to other distant sites of the body. Like pollen floating in the wind, these hardy microbes traverse and populate new foreign lands. Ultimately, the bacteria + macrophage pair will lodge within a tissue that attracts the attention of the immune response. This condition is known as EPTB, disseminated TB or miliary TB. Indeed, that pollen metaphor may not be too far from fact: the term “miliary TB” derives from the appearance of the small, discretely formed tuberculoid nodes on MRIs and X-rays as tiny millet seeds seasoned throughout the organ of its choice.

An unidentified man suffering from Pott's disease or extrapulmonary tuberculosis infection of the spine. Photo taken by John Mayall in 1877. Click for source.

EPTB can manifest itself in nearly every type of organ system of the body, though the most common sites are the lymph nodes, urinary tract and reproductive system, meninges of the brain, bones and joints, pleural cavity, skin, and peritoneal cavity. Some of these localized infections have acquired their own proprietary name: Pott’s disease for spinal TB, lupus vulgaris for TB of the skin, and scrofula for infected lymph nodes located in the neck/cervical region (or if you’re fancy: cervical tuberculous lymphadenopathy).

The point is: tuberculosis is not exclusively a respiratory disease but an opportunistic pathogen capable of infecting pretty much any organ in the body. It’s happy anywhere, sitting in its macrophagic throne pissing off the immune system with its infuriating presence and forming graulomas. It’s not only impressive but unique and weird.

A young unidentified patient with a case of scrofula or cervical tuberculous lymphadenopathy. Infection is characterized by abscess formation of the lymph nodes in the neck. Image: Images from the History of Medicine (IHM). Click for source.

It can get weirder: it seems that the serial monogamist King Henry VIII of England, as well as other less romantically inclined English and French monarchs between the 1200 to 1700s, had an intimate relationship with scrofula, the cervical lymphadenopathy form of TB (2). At the time, there existed a strong conviction that divinely appointed sovereigns could cash in on that holiness and, with a “royal touch”, cure scrofula sufferers. At the time, scrofula was considered any old disease with a prominent glandular presentation around the facial and cervical region, tuberculoid or not, and I imagine King Henry had quite the encyclopedic tour of illnesses (goiters! tumors! mumps!) during his time of curative prowess. Didn’t seem to do much of anything to temper his roving philandering eyes but, alas, libido is a powerful, powerful thing. As such, this quirk of history earned scrofula the moniker, the “King’s Evil”. Share that historical nugget at your next cocktail party!

EPTB can be tricky to diagnose as its a great disease mimicker, a lyrebird of an illness. Because the clinical presentation is so non-specific, so vague, it can be many years before a diagnosis of EPTB has definitively been made (3). Physicians must be on their toes in considering an individual’s risk factors for EPTB: history of travel, birthplace, ethnicity, sex and age. Aside from appearing most commonly in those infected with HIV/AIDS, it is also prevalent among young children and tends to infect women in greater numbers for unknown reasons .

As if we don’t already have to wonder about mites, toxoplasmosis and herpes lurking undetected in our bodies, now you can fret over possible extrapulmonary infection with that odd vagabond M. tuberculosis. You’re welcome.

Editor’s Note: Body Horrors has been quiet for the month of February in preparation for, celebration of and recuperation from Carnival Season and Mardi Gras in New Orleans, LA. My sincere apologies for my extended absence. If it makes you feel better, I was having the time of my life. I’m back now.

Resources

Wanna get deep into every clinical presentation of EPTB that has ever occurred? This exhaustive 38-page review is FREE with lots of pictures.

Jules Talrich was a popular anatomical model maker in the 1850s using wax and plaster to model various diseases and disfigurements. The Frenchman, who served as the official model maker for the Faculty of Medicine of Paris, currently has a number of his anatomical waxes peppered throughout medical museums around the world. This life-like wax model dating from the 1890s and now living at the National Museum of Health & Medicine in Washington, DC shows a man with a rather serious scrofula infection.

References

(1) Sharma SK & Mohan A. (2004) Extrapulmonary tuberculosis. Indian J Med Res. 120(4):316-53

(2) Barlow F. (1980 )The King’s Evil. Eng Hist Rev. 95(374): 3-27

(3) Dolberg OT, Schlaeffer F, Greene VW, & Alkan ML. (1991) Extrapulmonary Tuberculosis in an Immigrant Society: Clinical and Demographic Aspects of 92 Cases. Rev of Infect Dis. 13(1): 177-179

Dolberg OT, Schlaeffer F, Greene VW, & Alkan ML (1991). Extrapulmonary tuberculosis in an immigrant society: clinical and demographic aspects of 92 cases. Reviews of infectious diseases, 13 (1), 177-9 PMID: 2017620

Herpes Gladiatorum: Full Contact Infectious Diseases

In honor of one of the most lucrative American holidays happening this very weekend, I thought I’d explore sports and infectious diseases. Specifically, contact sports and skin infections! Since starting this blog, I’ve gathered that readers just love reading about transmissible skin infections, so what could be better than watching the Super Bowl and knowing just exactly what kind of diseases could possibly be smeared between the players of the Patriots and Giants?

There is a glut of infectious diseases that one can acquire from dabbling in combat or contact sports such as American or Aussie-style football, rugby, wrestling, and sumo. In fact, skin infections are the most common injury associated with all sports (1). All that body bashing and face-to-face smearing in contact sports does wonders for spreading skin or cutaneous infections. A number of these ailments are common to us non-athletic mortals – athlete’s foot, jock rash and ringworm (or tinea corporis). Two diseases in particular, with the marvelous potential to initiate larger epidemics within and beyond the locker room, form the focus of this article.

A 3d model of the herpes simplex virus 1 (HSV-1). Click for source.

Herpes gladiatorum is a wonderfully evocative name used to describe an athlete’s infection with herpes simplex virus 1 (HVS-1), a terribly contagious virus that many have the misfortune of being acquainted with; it’s estimated that 65% of people will become infected with the virus by the time they reach their 40s (2). Symptoms can include painful, blistery cold sores on the face and neck, along with a sore throat, infected lymph nodes and malaise.

It’s a tricky little bugger of a virus. It can remain dormant, hiding away in nerve cells known as sensory ganglia, only to spring out on one’s face or genitals during periods of physical or emotional stress or, say, when you’re sunbathing in tropical locales on vacation. It has an uncanny sense of knowing when to erupt at the most inappropriate of times, though I’ve been unable to track down any research examining the molecular basis of how it goes about conducting this remarkable mechanism.

A case of cold sores caused by oral herpes. Image: Samuel Freire da Silva, Dermatology Atlas. Click for source.

Most people rightfully assume that HSV-1 infection is a rather personal, intimate matter: we hear about transmission between a mother and her child, between romancing couples and so on. This makes sense considering that it’s spread by respiratory droplets or direct contact with infected lesions; you’ve really got to get up close and personal in someone’s face if you want to get a sense of what HSV-1 infection feels like (2). But given social situations with a generous amount of skin-to-skin contact with many individuals – sports, for instance – the virus will happily engage in a bit of unplanned host-hopping. As such, it has a frustrating tendency to erupt into outbreaks in sports team and during competitions.

Many athletes may sport micro-abrasions and skin breaks stemming from turf burns, powerful body-to-body collisions, facial stubble or beard burn, and shaving. Depending upon the level of protective clothing and gear, these athletes can experience substantial exposure with their opponent’s infected HSV-1 lesions, not to mention the respiratory droplets, spit and mucus that may transmit other types of infections. Charming! Among teammates, a grab-bag of infections can also be spread by sharing towels, water bottles, clothing, equipment, and hygiene and cosmetic products.

A rugby "scrum" maneuver, a rather efficient method of transmitting HSV-1. Click for source.

HSV-1 is considered to be particularly endemic in rugby players due to the style of the sport and the lack of protective gear (3). Its rampant presence in rugby leagues has earned it the moniker “herpes rugbiorum” or “scrum pox” (“scrum strep”, caused by the bacterium Streptococcus pyogenes, can also plague rugby players). In rugby, the “scrum” is a type of huddle maneuver used to return the ball into play. It is a sensational way to spread HSV-1: players in the forward position interlock their heads with their opponents in facing rows before the ball is launched between them. These forwards are the most likely of their teammates to contract scrum pox due to their prominent role in scrums and the increased prospect of serious face-to-face contact. The fact that rugby players do not use protective gear, including helmets, exposes a greater part of their body to physical contact and further increases their risk.

A herpes gladiatorum or HSV-1 rash on a high-school wrestler. Note that it is mostly localized to the right side of his face, suggesting that he is right-handed. Click for source.

HSV-1 regularly rears its ulcerous face on wrestlers as well. A research group checking serum samples from wrestlers to determine previous HSV 1 exposure found that 29.8% of college wrestlers had reported previous HSV infection (4). The level of intimacy required in grappling almost makes it inevitable that something is going to be transmitted between two athletes, whether that be sweat, saliva or HSV-1. Indeed, in a 1989 outbreak in high-school wrestling camp for boys, 34% of participants were diagnosed with HSV-1 (5). Lesions commonly appeared on regions of the body most likely to encounter direct skin-to-skin contact with their opponents – 73% on the head, 42% on the extremities and 28% on the trunk of the body. How do you tell if a wrestler is right or left-handed? Check which side of their face, head, neck and arms has the greatest amount of lesions. Athletes will tend to prominently use the most powerful sides of their body, regardless of which sport, and it will be this side that can receive the greatest amount of skin-to-skin contact with opponents.

Getting a touch of HSV-1 and sharing it with your teammates may be the least of an athlete’s problems. In 2003, a ghastly outbreak of methicillin-resistant Staphylococcus aureus (MRSA) emerged during a college football camp in Connecticut (6). Ten players were infected, of whom two required hospitalization. The infection was discovered to have spread due to the combination of body shaving and turf burns from the artificial grass. Infections were most commonly located at the elbow, thigh, hip, chin, forearm and knee, parts of the body most likely to incur abrasions on the turf. Those players with turf burns had a seven-fold risk of acquiring MRSA infection than those who emerged from scrimmage and active play unscathed (6). Cornerbacks and wide receivers were particularly susceptible due to their frequent body contact during drills and scrimmage play.

A quick browse through the research literature pulls up dozens of MRSA outbreaks like this. In 2002, two college football players in Los Angeles were hospitalized due to MRSA infection (7). A one-year surveillance of a football team at a unnamed major university in the southeastern United States found that 19% of the players showed evidence of nasal colonization of the bacteria at the end of the football season; though the high prevalence of MRSA among these men did not yield any active skin and soft tissue infections, it goes to show how endemic of a problem this really is (8). In 2007, six football players on a Brooklyn high school football team showed evidence of MRSA skin and soft tissue infection; the players had just recently returned from a preseason training camp (9). The infections were serious enough that they generated abscesses requiring surgical incision and drainage.

An infected ulcer caused by methicillin resistant Staphylococcus aureus (MRSA). Image: Dermatlas, Johns Hopkins University. Click for source.

MRSA colonization of football players is apparently becoming so commonplace that some researchers have suggested using them as human sentinels for public health surveillance of outbreaks within the surrounding community (10). It is regrettably becoming a rather conventional type of emerging infection in athletes.

These infections aren’t just unseemly looking but can be disfiguring, have long-lasting effects within the body and can temporarily disqualify an athlete from practice and competition to prevent localized outbreaks. Hell, some of them can kill ya! These outbreaks can ruin seasons for the team while for salaried athletes, these kinds of infections have serious economic, professional and personal repercussions. Medical professionals recommend that players abstain from play until they’ve started antiviral medications or antibiotics, they are free of systemic symptoms – fever, malaise and lymph node swelling – and until any moist lesions have subsided. Seems reasonable, no?

Infectious diseases are always context specific and spread through particular practices. In the case of contact sports, there are several variables at play that help to spread some nasty infections. While there isn’t a lot we can do about changing how a sport is played (or can we?), coaches and referees can keep an eye out for athletes who seem ill or are showing visible evidence of infection. Fighting against poor hygiene practices and ensuring that wounds are cleaned and dressed immediately can also keep these kinds of sticky situations in line. Game on!

RESOURCES
A mission statement and guidelines on how to deal with herpes gladiatorum from the Sports Medicine Advisory Committee at the National Federation of State High School Associations.

Wrestlers filed a “herpes lawsuit” in 2008 against their coach and trainer holding them responsible for a localized HSV-1 outbreak.

In 2008, researchers discovered a unique herpes strain that only affects sumo wrestlers. Neat!

REFERENCES
1. BB Adams. (2010) Skin Infections in Athletes. Expert Rev Dermatol. 5(5): 567-577
2. R Sharma et al. (2011) Herpes Simplex in Emergency Medicine. Accessed online on Feb 2, 2012. Link.
3. BB Adams. (2000) Transmission of cutaneous infections in athletes. Br J Sports Med. 34(6): 413–414
4. B.J. Anderson (2008) Managing Herpes Gladiatorum Outbreaks in Competitive Wrestling: The 2007 Minnesota Experience. Curr Sports Med Rep. 7(6): 323-7
5. Belongia EA, Goodman JL, Holland EJ, et al. (1991) An outbreak of herpes gladiatorum at a high-school wrestling camp. N Engl J Med. 325(13): 906-10
6. EM Begier et al. (2004) A High-Morbidity Outbreak of Methicillin-Resistant Staphylococcus aureus among Players on a College Football Team, Facilitated by Cosmetic Body Shaving and Turf Burns. Clin Infect Dis. 39(10): 1446-1453
7. DM Nguyen et al. (2005) Recurring Methicillin-resistant Staphylococcus aureus Infections in a Football Team Emerg Infect Dis. 11(4): 526-32
8. CB Creech (2010) One-year surveillance of methicillin-resistant Staphylococcus aureus nasal colonization and skin and soft tissue infections in collegiate athletes. Arch Pediatr Adolesc Med. 164(7): 615-20
9. Centers for Disease Control & Prevention (CDC). (2009) Methicillin-resistant Staphylococcus aureus among players on a high school football team–New York City, 2007. MMWR Morb Mortal Wkly Rep. 58(3): 52-5
10. B Barr, M Felkner & PM Diamond. (2006) High school athletic departments as sentinel surveillance sites for community-associated methicillin-resistant staphylococcal infections. Tex Med. 102(4):56-61

Adams, B. (2010). Skin infections in athletes Expert Review of Dermatology, 5 (5), 567-577 DOI: 10.1586/edm.10.50